ArticleThe journal of pathology. Clinical research2020
Frequent alterations in p16/CDKN2A identified by immunohistochemistry and FISH in chordoma.
Article in The journal of pathology. Clinical research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 56 citations in OpenAlex.
- Review
- From Histology to Multi-Omics: Review of Chordoma Classification and Its Clinical Implications.Cells · 2026Review
- Mutational analysis of primary and advanced chordoma tissue using next-generation sequencing.Cancer · 2025Article
- The TBXT rs2305089 SNP links the benign notochordal cell tumour and chordoma.The Journal of pathology · 2025Article
- Cuproptosis in lung cancer: mechanisms and therapeutic potential.Molecular and cellular biochemistry · 2024Review
- A retrospective study on the mechanism underlying quick transfer from response to resistance in a repeated recurrent chordoma patient with molecular alterations treated with Palbociclib.Journal of cancer research and clinical oncology · 2024Article
- Construction of a prognosis model of head and neck squamous cell carcinoma pyroptosis and an analysis of immuno-phenotyping based on bioinformatics.Translational cancer research · 2024Article
- FISH analysis reveals CDKN2A and IFNA14 co-deletion is heterogeneous and is a prominent feature of glioblastoma.Brain tumor pathology · 2024Article
- Review
- A chance to cut is a chance to cure: complete resection of an atypical neurofibroma prevents further progression to malignancy.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2023Article
- DNA methylation, combined with RNA sequencing, provide novel insight into molecular classification of chordomas and their microenvironment.Acta neuropathologica communications · 2023Article
- Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas.Acta neuropathologica · 2023Article
- Prognostic Relevance and In Vitro Targeting of Concomitant PTEN and p16 Deficiency in Chordomas.Cancers · 2023Article
- Article
- Aberrant paracrine signalling for bone remodelling underlies the mutant histone-driven giant cell tumour of bone.Cell death and differentiation · 2022Article
- Single-cell transcriptome profiling reveals intra-tumoral heterogeneity in human chordomas.Cancer immunology, immunotherapy : CII · 2022Article
- Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion.Biomedical reports · 2022Article
- Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma.Nature communications · 2022Article
- Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Nasal Cavity, Paranasal Sinuses and Skull Base.Head and neck pathology · 2022Review
- Emerging target discovery and drug repurposing opportunities in chordoma.Frontiers in oncology · 2022Review
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The expression of p16/CDKN2A, the second most commonly inactivated tumour suppressor gene in cancer, is lost in the majority of chordomas. However, the mechanism(s) leading to its inactivation and contribution to disease progression have only been partially addressed using small patient cohorts. We studied 384 chordoma samples from 320 patients by immunohistochemistry and found that p16 protein was lost in 53% of chordomas and was heterogeneously expressed in these tumours. To determine if CDKN2A copy number loss could explain the absence of p16 protein expression we performed fluorescence in situ hybridisation (FISH) for CDKN2A on consecutive tissue sections. CDKN2A copy number status was altered in 168 of 274 (61%) of samples and copy number loss was the most frequent alteration acquired during clinical disease progression. CDKN2A homozygous deletion was always associated with p16 protein loss but only accounted for 33% of the p16-negative cases. The remaining immunonegative cases were associated with disomy (27%), monosomy (12%), heterozygous loss (20%) and copy number gain (7%) of CDKN2A, supporting the hypothesis that loss of protein expression might be achieved via epigenetic or post-transcriptional regulatory mechanisms. We identified that mRNA levels were comparable in tumours with and without p16 protein expression, but other events including DNA promoter hypermethylation, copy number neutral loss of heterozygosity and expression of candidate microRNAs previously implicated in the regulation of CDKN2A expression were not identified to explain the protein loss. The data argue that p16 loss in chordoma is commonly caused by a post-transcriptional regulatory mechanism that is yet to be defined.
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